Risk factors for pancreas cancer are not well established. Because of its near uniform and rapid case fatality, most studies of pancreas cancer have been small, had modest response rates and/or collected data exclusively from a surrogate respondent, and had limited, if any, biologic samples for molecular analysis. The long-term goal of this project is to investigate a wide range of environmental and genetic factors in order to improve our understanding of pancreas cancer etiology, beginning with a large, case-control study based on direct participant interview, electronic medical record review and blood sampling. We propose to conduct a case-control study of pancreas cancer, comprised of 745 cases and 745 controls in the defined populations of two health maintenance organizations (HMO) that have computerized administrative and clinical data to support "ultra-rapid" case identification within ten working days of diagnosis. To maximize statistical power to investigate differences in risk by race, we will assemble a second control group of 296 African-Americans matched to the expected 74 African- American cases using a 4:1 ratio. Given the large effort required to assemble these data, we propose to address an extensive set of specific aims: 1) To investigate the relation between diabetes and pancreas cancer risk, focusing on age at diabetes onset and type of diabetes, based on interview and electronic medical record data;2) To investigate the relation between pancreas cancer and diet focusing on factors that influence insulin resistance and factors that influence methyl group availability;3) To investigate the relation between use of non-steroidal anti-inflammatory drugs and pancreas cancer risk;4) To investigate the relation between direct and environmental exposure to tobacco and pancreas cancer risk;5) To characterize the familial aggregation of pancreas cancer;and 6) To establish a study biorepository for use in future studies of genetic polymorphisms, biomarkers, and gene-environment interactions in relation to risk of pancreas cancer. The proposed study will result in a large sample of newly diagnosed cases and will establish a unique and comprehensive resource for future epidemiologic, molecular, and genetic investigations. Results from this study will lead to improved understanding of pancreas cancer risk factors and the molecular events leading to the development of pancreas cancer, which are both imperative for effective strategies for prevention and early diagnosis.